Polymorphisms of the CYP1A1, CYP2E1 and XRCC1 genes and cancer risk in a Southern Italian population: a case-control study (original) (raw)
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Investigation of CYP1B1*3 and CYP1B1*4 polymorphisms in a Turkish population
Health Sciences Quarterly
CYP1B1 is a P450 enzyme involved in activating pro-carcinogens to carcinogens as well as estrogen metabolism. In order to examine the effect of CYP1B1 on cancer metabolism, it should be compared with healthy individuals and whether the polymorphism between healthy individuals and sick individuals is significant. This study aims to screen the CYP1B1*3 and CYP1B1*4 polymorphisms of a group of individuals who have not been diagnosed with cancer to examine the genetic differences of metabolic enzymes in the Turkish population.This study is a cross-sectional type descriptive study.The study included 295 patients without a cancer diagnosis. The research sample includes patients who applied to Ankara University Medical Faculty Hospital and Afyonkarahisar Health Sciences University Research and Application Hospital. The individuals signed voluntary consent forms before participation, and 3 ml blood samples were taken from each. DNA samples were obtained using a DNA isolation kit, and then p...
Introduction: Genes encoding xenobiotic metabolizing enzymes especially CYP1A2 play an important role in determining the out come of carcinogen exposure and Colorectal Cancer susceptibility risk. Functional polymorphisms of G3860A, T739G and C729T of CYP1A2 gene have been identifi ed. Aims A case control study was designed to genotype the Malaysian normal controls and CRC patients to determine the variant allele frequencies of three polymorphisms of CYP1A2 and to evaluate whether variant genotype has any association either singly or in combination with CRC susceptibility risk. Material & method Genotyping of the 3 polymorphisms (G3860A, T739A & C729T) CYP1A2 genes was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) on 111 sporadic histopathologically confirmed CRC patients and 123 normal healthy controls. Result When the 3 polymorphisms G3860A, T739G and C729T were analyzed singly, there was no signifi cant association. When the risk association was evaluated using combination genotypes, the combination of G3860A / T739T genotype showed statistically signifi cant risk with OR 1.75.
Cytochrome P450 1A1 genetic polymorphisms as cancer biomarkers
Indian Journal of Cancer, 2015
Phase I metabolic enzyme CYP1A1 plays an important role in xenobiotics metabolism and has been extensively studied as a cancer risk biomarker. CYP1A1 is polymorphic and its four variants, e.g., CYP1A1* 2 A, CYP1A1* 2C, CYP1A1* 3 and CYP1A1* 4 with trivial names m1, m2, m3, and m4 respectively, are most commonly studied for cancer link. Gene-gene interaction studies combining polymorphisms of this enzyme with those of phase II detoxifying enzymes, especially glutathione S-transferases (GSTs) revealed greater risk for cancer susceptibility. Variants of CYP1A1 have also been found to be associated with chemotherapeutic adverse-effects. Results of these studies, however, remained largely contradictory mainly because of lack of statistical power due to involvement of small sample size. Strongly powered experimental designs involving gene-gene, gene-environment interactions are required in order to validate CYP1A1 as reliable cancer-biomarker.
The Effect of the CYP1A1*2A Allele on Colorectal Cancer Susceptibility in a British Population
Genetic testing and molecular biomarkers, 2016
Colorectal cancer (CRC) is a major health problem despite some recent improvements in overall survival. Genetic polymorphisms affecting carcinogen biotransformation or DNA repair play pivotal roles in the carcinogenesis process. CYP1A1*2A (6235 T/C, rs4646903, MspI) is thought to be associated with an increased risk of CRC because of its role in metabolic activation of polycyclic aromatic hydrocarbons; however, the results of previous studies are conflicting. In this study, a possible association between the CYP1A1*2A allele and CRC and the effect of cigarette smoking on this risk in a British population were examined. A prospective case-control study including 200 cases and 254 age-sex-matched controls was conducted with British participants from north-east of England. Genotyping of CYP1A1*2A was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. CYP1A1*2A was not associated with CRC development odds ratio (OR = 1.566; 95% confide...
Variant alleles of the CYP1B1 gene are associated with colorectal cancer susceptibility
BMC Cancer, 2010
Background: CYP1B1 is a P450 enzyme which is involved in the activation of pro-carcinogens to carcinogens as well as sex hormone metabolism. Because differences in the activity of the enzyme have been correlated with variant alleles of single nucleotide polymorphisms (SNPs), it represents an attractive candidate gene for studies into colorectal cancer susceptibility.
Association of CYP1B1 genetic polymorphism with incidence to breast and lung cancer
Pharmacogenetics, 2000
Cytochrome P450 1B1 (CYP1B1) participates in the metabolic activation of a number of procarcinogens including benzo[a]pyrene and the hydroxylation of 17â-estradiol at the C-4 position. In this study, we investigated the association between CYP1B1 genetic polymorphism and breast or lung cancer incidence. The Ala-Ser polymorphism at codon 119 in presumed substrate recognition site 1 was signi®cantly associated with the incidence of breast or squamous cell carcinoma of the lung. On the other hand, Leu-Val polymorphism at codon 432 did not show any association to the cancers. An allele containing both Ala and Leu simultaneously, comprised 75% of alleles among 315 Japanese healthy controls, was signi®cantly inversely associated with breast cancer incidence. When expressed in a recombinant system, this CYP1B1 cDNA showed the lowest 17â-estradiol 4-hydroxylase activity among four different variant forms of CYP1B1. Thus, inter-individual differences in activation of procarcinogens or metabolism of oestrogen originating from genetic polymorphisms of the human CYP1B1 gene may contribute to the susceptibility of human cancers.
Genetic polymorphism of cytochrome P450 2E1 in the Turkish population
Cell Biochemistry and Function, 2001
CYP 2E1 is involved in metabolic activation of carcinogenic N-nitrosamines, benzene, urethane and other low molecular weight compounds. CYP2E1 gene is present in the population in various polymorphic forms. We detected the RFLP of the human CYP2E1 gene with the restriction endonuclease PstI, RsaI and DraI in a group of 153 Turkish individuals. According to the results of the PstI/RsaI analysis, 96.07% of the subjects were of the c1/c1 genotype, and 3.93% were of the c1/c2 genotype. In the DraI RFLP analysis, 84.30% DD genotype, 15.03% CD genotype and 0.66% CC genotype were determined. The data obtained may be useful in epidemiological studies of the in¯uence of CYP2E1 polymorphism on carcinogenesis.
Archives of Industrial Hygiene and Toxicology, 2009
Genetic Polymorphism of Metabolic Enzymes P450 (CYP) as a Susceptibility Factor for Drug Response, Toxicity, and Cancer RiskThe polymorphic P450 (CYP) enzyme superfamily is the most important system involved in the biotransformation of many endogenous and exogenous substances including drugs, toxins, and carcinogens. Genotyping forCYPpolymorphisms provides important genetic information that help to understand the effects of xenobiotics on human body. For drug metabolism, the most important polymorphisms are those of the genes coding for CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5, which can result in therapeutic failure or severe adverse reactions. Genes coding for CYP1A1, CYP1A2, CYP1B1, and CYP2E1 are among the most responsible for the biotransformation of chemicals, especially for the metabolic activation of pre-carcinogens. There is evidence of association between gene polymorphism and cancer susceptibility. Pathways of carcinogen metabolism are complex, and are mediated by activities...